Another HIV Tivicay Birth Outcome: Better Infant Survival

Infants born to women with HIV who were taking dolutegravir (DTG) plus emtracitabine/tenofovir alafenamide (FTC/TAF) had significantly higher odds of surviving the first 6 months after delivery than infants born to women taking efavirenz-based regimens.

“When one wants to start ART [antiretroviral treatment] in pregnancy, dolutegravir-containing regimens should be preferable over efavirenz-based regimens,” said Lamick Chenula, MD, of Project Malawi, University of North Carolina at Chapel HIll, who presented the data at the Conference on Retroviruses and Opportunistic Infections (CROI) 2021 Annual Meeting. “Our study findings provide additional reassuring data for use of DTG and TAF during pregnancy and post partum.”

The IMPAACT 2010 trial also showed that women who took the regimen during pregnancy were less likely to need to switch because of virologic failure. Together, the data add to mounting evidence of better outcomes for women living with HIV and infants born to those women when women begin taking dolutegravir after conception. This comes after a study from 2018 suggested that taking dolutegravir at conception might be associated with greater risk for neural tube defects in infants. That concern has waned since then.

Chenula reported primary pregnancy results from IMPAACT 2010 last year showing that women receiving dolutegravir-containing ART were more likely to experience viral suppression and fewer side effects than women taking efavirenz-containing regimens. This year, researchers presented data meant to show whether those positive results with dolutegravir could be maintained 50 weeks post partum.

This is important, especially in Africa, because efavirenz continued to be the World Health Organization’s recommended treatment until 2019. In the United States, dolutegravir did not become the preferred treatment option during pregnancy until the end of 2020.

In the main trial, 643 women aged 14 to 28 years who were living with HIV and who were at least 14 weeks’ pregnant were randomly assigned to receive dolutegravir plus emtracitabine and TAF; dolutegravir plus emtracitabine and TDF; or efavirenz plus emtracitabine and TDF.

Women were qualified for the trial if they were living with HIV, were between 14 and 28 weeks’ gestation, and had been taking any antiretroviral treatment for 2 weeks or less at the start of the trial. That meant that the women had been receiving their regimens for at least 12 weeks before delivery. Women continued to take those regimens for 50 weeks or until virologic failure. The trial was conducted in nine countries: Brazil, Botswana, India, South Africa, the United States, Tanzania, Thailand, Uganda, and Zimbabwe.

After delivery, women and infants were tracked for adverse events, infant mortality, and infant HIV infection. In addition, the women in the trial were regularly tested for viral load. The study considered a woman to have an undetectable viral load if testing showed ≤200 or fewer copies/mL of the virus.

Of the 643 women enrolled in the trial, the median age was 26; the women started the trial at a median of 21.9 weeks into pregnancy — well into the second trimester. At the start of the trial, women had been receiving HIV treatment for only 6 days; the median HIV viral load was 903, and the median CD4 count was 466.

Infant Mortality

Of 617 live births, 20 of those infants did not survive to 50 weeks. Most of those deaths (15) occurred within the first 28 days after delivery. Most of the deaths were due to prematurity, sepsis, and infections. Because there were so few deaths, Chenula said the team had not analyzed cause of death by treatment arm.

They did find that efavirenz-based ART was more likely to be associated with infant death: 3% of infants born to women who used any dolutegravir-based regimen died in the first 6 months, compared to 6.9% of infants born to women who used efavirenz during pregnancy and post partum (P = .008).

In an analysis that compared specific dolutegravir regimen with efavirenz, survival was even better in babies born to women who received dolutegravir and TAF. Only 1% of those infants died in the first 6 months, compared to 2% in the dolutegravir and TDF-containing arm. Death among infants born to women taking efavirenz remained at 6.9% (P = .0001.)

In the dolutegravir arms, two infants were born with birth defects (atrial septal defect and talipes equinovarus of the right foot). In the efavirenz arm, two were born with birth defects (duodenal atresia/ileal stenosis and subgaleal cyst).

When stillbirths were considered, the risk for death among babies born to women taking DTG and TAF was still about 1.5 times lower than among infants born to women taking efavirenz (4.6% vs 8.5%).

Four infants acquired HIV during the trial, two to mothers in the dolutegravir and TAF arm, one to a mother receiving dolutegravir and TDF-containing ART, and one in the efavirenz arm. All were breastfed and acquired HIV despite receiving ART prophylaxis. This led CROI attendees to suggest that the transmissions could be the result of breastfeeding. Current US perinatal guidelines discourage breastfeeding but allow for shared decision making.

Maternal viral load accounted for one transmission, which occurred in a woman taking dolutegravir and TAF whose viral load was >9000 copies/mL at all study visits. But not all transmissions could be explained by high viral load. In the second woman who received dolutegravir and TAF, the maximum viral load was 42 copies/mL through delivery. For a woman taking dolutegravir and the TDF-containing regimen, the viral load was <40 copies/mL by week 8 of the study and stayed there.

For the woman who received efavirenz, HIV RNA was >40 copies/mL through week 26, but there was no record of viral load at week 50, at which point the infant tested positive for HIV.

But Chenula added, “There were no apparent differences in estimated probability of infant HIV infection between study arms.”

Good for Women

Both dolutegravir and efavirenz resulted in extremely high levels of viral suppression for the women, but dolutegravir did come out on top regarding rates of virologic failure, defined as two successive HIV viral load tests of ≥200 copies at or after 24 weeks of treatment. This was true regarding dolutegravir-containing regimen with efavirenz (P = .04), but the difference was particularly marked for women taking dolutegravir plus FTC/TAF (4.1%) compared to women taking efavirenz (10.4%) (P = .012).

“The efavirenz arm also had significantly more women who changed treatment due to virologic failure or drug resistance, whereas [dolutegravir]-containing regimens were modified mostly due to fertility choices,” Chenula said.

The Ongoing Weight Question

But it wasn’t all good news. Women who received dolutegravir and FTC/TAF experienced significantly more weight gain — although in this study, weight gain was associated with fewer adverse events, rather than more. Chenula cautioned that weight gain should “be interpreted carefully.”

“We did see higher weight gain in women on DTG, especially when combined with TAF,” Chenula told Medscape Medical News, “but that regimen also had the best pregnancy outcomes.”

All this means that clinicians shouldn’t rule out dolutegravir in pregnancy because of early signs of neural tube defects, Shahin Lockman, MD, Brigham and Women’s Hospital, Boston, Massachusetts, told Medscape Medical News.

Indeed, she and Chenula said that these results provide more evidence that women, not clinicians, should decide what regimen they should take during pregnancy.

“Really, as clinicians, the best we can do is provide the information and support to women to help them make an informed decision and share the decision-making process,” she said.

Conference on Retroviruses and Opportunistic Infections (CROI) 2021 Annual Meeting: Abstract 177. Presented March 10, 2021.

Heather Boerner is a science and medical reporter based in Pittsburgh, PA and can be found on Twitter at @HeatherBoerner. Her book, Positively Negative: Love, Sex, and Science’s Surprising Victory Over HIV, came out in 2014.

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